Trials funded by rich patients could help find cures for us all

Bridging gaps in medical funding. Patrick Feller

Disease can affect any person, rich or poor. While your bank balance can’t really protect you from getting sick, it could potentially buy you – and many other patients – access to a better treatment for your disease. A new “plutocratic proposal” put forward by Alexander Masters enlists wealthy patients to both fund and participate in clinical trials alongside other patients who could benefit from an otherwise untested new treatment.

Developing a new treatment can be a long and expensive process that leaves promising new treatments languishing in a lab freezer. The translation of a treatment from the lab bench into humans can cost millions or billions of dollars. There are few grants that suit this type of research translation – and private donations, while very gratefully received, rarely add up to the right numbers.

If it is a disease that affects many, like cancer, then huge organisations, such as Cancer Research UK, can help lobby for grants to be directed towards clinical trials that will, on average, help more people. In such economic circumstances, those with rare diseases have a hard case to make for money to be directed their way.

This funding situation is only expected to get worse. For instance, the Canadian Institutes for Health Research (CIHR), one of Canada’s largest funding bodies for health sciences, is debating whether clinical trials should be funded at all. They argue that funding a single clinical trial with a price tag of C$2m (US$1.8m) – the approximate cost for an academic researcher to run their own early-stage study – would mean that many other research labs who might otherwise expect to receive smaller grants to support their basic research would miss out.

The main alternative path for finding funds to take that first step into a clinical trial pairs a researcher with a pharmaceutical company. The industrial partner supplies the necessary funds needed to run the study, as long as they see good potential for a return on their investment. The downside is that researchers usually end up signing away their promising treatment as a condition of the partnership – and ultimately losing control of subsequent returns should the therapy prove to be successful.

With Masters’ proposal, a rich benefactor essentially enables a clinical trial to go ahead that would otherwise have remained unfunded. The idea involves creating a not-for-profit “dating agency” that would match a sick benefactor with a researcher who has a promising new treatment for his or her disease.

The dating agency would have an independent panel of scientists whose job it would be to validate the science behind the therapy. The rich benefactor donates, say, US$2m and both the benefactor and 19 other people suffering from that disease, who could not have afforded to pay a contribution towards such a trial, get a spot on the clinical trial. The framework of the clinical trial – including ethical and regulatory approval – remains unchanged. The only difference is where the funds are coming from.

One version of Alexander Masters’s proposal. The Wellcome Trust/Peta Bell/Jean Jullien

Most importantly, Masters has shown that this funding approach works. After his close friend Dido Davies died from cancer after receiving traditional treatments that didn’t really help, Masters began exploring new ways to help patients get access to promising new drugs.

In just eight months, he had helped to secure £2m (US$3.2m) to get a new biotherapy for neuroendocrine cancer – Dido’s disease and the one that killed Steve Jobs – into clinical trials. This new biotherapy, a cancer-killing adenovirus developed in Uppsala University in Sweden, had been languishing in a freezer for several years because of a lack of funds.

Masters explains his idea:

There are 100,000 people in the world worth more than £20m (US$32m). According to the medical statistics, between three and five people in every 100,000 will get neuroendocrine cancer. So three to five supremely wealthy people will have the disease. For £1m, I was going to sell one or two of these wealthy individuals a place on the [biotherapy] trial. All the wealthy individuals had to do was pay for the entire trial.

Masters initially held a crowdfunding campaign to raise £200,000 (US$320,000) and generate enough publicity for his idea. As he had hoped, the campaign caught the attention of an American millionaire called Vince Hamilton, who was also suffering from neuroendocrine cancer. He supplied Uppsala University with the remaining funds to start the clinical trial.

Masters now hopes that this model can fund further trials. One of the golden features of his idea is that it shifts the return on clinical trials from profit – the aim of pharmaceutical industry-funded trials – to health. Masters’ new idea appears to be a scalable solution that could see plutocratic patients overhauling the currently listless clinical trial funding structure.

Originally published with The Conversation UK

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Tracking the Daily Microbiome

human microbiome by Hank Osuna

Human Microbiome by Hank Osuna

Humans are essentially 90% bacteria. These bacteria pepper our skin and hang out in our digestive tracts, helping to break down complex carbohydrates and keeping bad bugs in check.

We know how the human microbiome (our collection of bacteria) gets seeded during the birth process, and we know how bacterial populations change in the aftermath of a biological apocalyse, such as their human host taking a course of antibiotics. Yet we know very little about how the microbiome changes on a day-to-day basis.

Now, a team of scientists at Massachussetts Institute of Technology (MIT) have changed that by recruiting two individuals to provide samples of their poop and saliva every day for a YEAR to track their gut and oral microbiome signatures, and correlate them with lifestyle and activities.

Overall, microbe communities remained remarkably stable for months at a time. The three big variables – sleep, exercise and mood – failed to make much of an impact on microbe populations. Yet small dietary and lifestyle changes prompted rapid (next day) changes. Increasing fibre intake boosted populations of fibre-sensitive Bifidobacteria, Roseburia and Eubacteria. Bifidobacteria levels were similarly enhanced after eating live yoghurt cultures. Eating citrus fruits led to a jump in levels of Clostridiales bacteria, while dental flossing decreased saliva levels of the dental pathogen, Streptococcus mutans.

bacterial bodies bryan christie scientific american june 2012

Bacterial Bodies by Bryan Christie

The biggest changes in microbiome signatures happened in the wake of relatively rare life events. Travelling from a developed to a developing country caused numbers of Bacteriodes microbes to swell (as the host ate new foods) and increased Proteobacteria populations (as the host experienced bouts of diarrhea). These bacteria settled back down to normal levels when their host returned home. On the flip side, a bout of Salmonella food poisoning permanently wiped out a subset of native Firmicutes bacteria, which eventually got replaced by other similar species.

It appears, then, that our microbes generally go about their business in a happy, unpeturbed state. Yet inadvertently introducing them to a new experience can either result in a benevolent (often temporary) change, or a tremendously negative wipe-out event.

You can read the original #openaccess article free here.

David LA, Materna AC, Friedman J, Campos-Baptista MI, Blackburn MC, Perrotta A, Erdman SE, & Alm EJ (2014). Host lifestyle affects human microbiota on daily timescales. Genome biology, 15 (7) PMID: 25146375

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Plastic bags responsible for outrageous lack of cute pink piglets

Margaret Ackland, Plastic Bag, Oil on Linen

Margaret Ackland, Plastic Bag, Oil on Linen

Most of us now subscribe to the idea that plastic bags are bad for the environment. Hence, droves of people turn up at their local supermarket with a sturdy jute bag in tow. Now, there’s evidence that the items that get placed into plastic bags also have a terrible time, especially if they’re biological in origin.

Take the case of pig farmers in Spain. In Spring 2010, 41 farms across Spain reported issues with their lady pigs failing to get pregnant after artificial insemination. The ensuing biological detective hunt found that sperm quality was high (it was good and wriggly, and donated from several different boars, ruling out a genetic incompatibility) and the fertility of the potential mother pigs was good. All the animals were in good health, and they were kept in comfortable, well-fed conditions.

One of the factors that all the farms had in common was the brand of plastic bag being used to store the boar semen until it got pumped into the lady pig. In fact, the longer the semen was kept in these bags, the greater the decrease in fertility.


Plastic bags: a chemical cocktail

Concerned that a chemical contaminant may be to blame, scientists at the Universidad de Zaragoza passed an old batch of “good” bags and a new batch of “suspicious” bags through a mass spectrometer (a machine that breaks materials up into their chemical components). They found that the “suspicious” bags contained five extra chemicals that weren’t present in the “good” bags: 1) octyl phthalate, 2) 13-docosenamide, 3) BADGE (a derivative of Bisphenol A), 4) 1,4-trioxacyclotridecane-8,13-dione (a cyclic lactone) and 5) diethylene glycol cyclic phthalate. These chemicals formed part of the adhesive used to manufacture the multilayer bags.

Three of these chemicals (BADGE, 1,4-trioxacyclotridecane-8,13-dione and diethylene glycol cyclic phthalate) were actually capable of leaching out of the bags into the fluid they contained (sterile water was used as a less messy substitute for boar semen to find this out). Yet in a dish, mixing these three chemicals with boar semen had no impact on sperm quality: no obvious abnormalities were seen, and the sperm were still able to penetrate eggs in a fish.

Finally, the ultimate test was performed: if semen spiked with these three chemicals was infused into a lady pig, would there be an outrageous lack of cute pink piglets born? Sure enough, there was a drop in the fertility rate from 84% to 58%, and the number of piglets being born fell from 231 to 70.

About your plastic water bottle…

This study didn’t go as far as identifying exactly how these chemicals were messing up fertilisation: the authors speculated that blastocyst implantation or early development may have been affected. However it happened, though, this is definitely a cautionary tale for using plastic bags as storage containers, with significant relevance for human artificial insemination. The leaching of such chemicals into the environment as plastic bags break down on landfill remains a sure source of concern to humans and pigs alike.

Nerin C, Ubeda JL, Alfaro P, Dahmani Y, Aznar M, Canellas E, & Ausejo R (2014). Compounds from multilayer plastic bags cause reproductive failures in artificial insemination. Scientific reports, 4 PMID: 24810330

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The science behind FIFA’s footballs

Football_soccer_futbol_by_walexxx19Lovers and haters of the World Cup alike can’t fail to be amazed by the skills of some professional footballers. Like David Beckham or Cristiano Ronaldo. But while some footballers have been blessed by biology, it’s not just the combined genetic talent of a player or a team that leads to a stunning win or a sorry loss. According to scientists at the University of Tsukuba in Japan, the aerodynamic performance of a football can introduce a skill set all of its own.

The football has evolved substantially from its vaguely nauseating origins (an inflated sheep’s bladder) to the shiny polished orb in use today. A typical football is made from 32 five- and six-sided panels stitched together to form a pleasingly spherical shape. In recent years, this basic design has developed towards minimising the number of panels and changing the pattern in which they’re stitched together to boost aerodynamic performance and consistency. Adidas, who ride at the forefront of innovative football design, have created the Cafusa (32 panels; currently used by many football leagues), the Teamgeist 2 (14 panels; the official ball of the 2008 EURO cup) and the Jabulani (8 panels; the official ball of the 2010 FIFA World Cup). Now, for the FIFA World Cup 2014, they’ve made it to the 6 panel ball: the Brazuca.

The team of Japanese scientists wanted to find out how these different balls – the Cafusa, Teamgeist 2, Jabulani, Brazuca and the traditional Molten Vantaggio 32-panel ball – behaved in flight, and how this affected shot accuracy on goal. To do this, they employed a wind tunnel, a kick robot and a whole bagful of beautiful balls. To take into account the difference in panel stitching design, they looked at the ball’s performance when it was kicked off from two orientations: normal (head on) or tilted 180 degrees (see below).


They found that the different balls experienced substantially different aerodynamic forces as they were “kicked” into the wind tunnel. The Brazuca was the most stable ball in flight, followed by the conventional ball, Cafusa, Teamgeist 2 and Jabulani.

When the balls were travelling at higher speeds (the equivalent of a good hearty kick, or a “power shot”), the Cafusa generated the biggest increase in lift and side force – which could allow the ball to travel a greater distance. The Jabulani put in the worst performance in this category, and behaved “irregularly” when it was in flight.

The scientists then launched balls from both orientations at 30m/s towards a goal 25m away, and plotted the hits on target (see graphs below; blue is head on, red is tilted 180°). The Brazuca and the conventional ball gave the best performances, hitting the target most consistently regardless of the orientation of the ball (the blue and red spots cluster together). For the Cafusa, the Jabulani and the Teamgeist 2, the flight paths and in-flight behaviour varied hugely depending on which orientation the ball was in when it set off towards the goal (the blue and red spots are far apart). Even when the number of panels were the same (Cafusa vs. Conventional ball; both 32 panels), differences in panel orientation and stitching design meant the conventional ball hit the target more consistently than the Cafusa.

accuracy on goalThese results – particularly the importance of panel orientation on performance – will undoubtedly be used to inform the design of the next generation of footballs with an eye to improving shooting accuracy and enhancing player performance. Ultimately, though, the conventional 32 panel ball performed just as well – if not better – than most of the innovative new footballs tested, suggesting that at some point it’s not that easy to improve upon design perfection.

Hong S, & Asai T (2014). Effect of panel shape of soccer ball on its flight characteristics. Scientific reports, 4 PMID: 24875291

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Watching it Burn: Soil Microbes vs. Wildfires

Los Angeles County "Station Fire" view from LAXWildfires can devastate ecosystems across the world. In 2012, over 67,000 wildfires raced across more than 9 million acres of land in the US alone. Fuelled by wind and parched vegetation, wildfires burn through everything in their path: plants don’t stand a chance, and even mobile animals struggle to outpace the flames.

But what impact do wildfires have on the beasties that live deep down in the soil? For example, soil-dwelling microbes, like bacteria? These incredibly important organisms help ecosystems to flourish, but their ability to recover after a forest fire – and to help other parts of the ecosystem recover, too – has been largely uncharacterised. Until now.

A team of scientists in China recently calculated that 70-80% of soil microbial biomass (the organic material made up of bacteria and fungi) was lost after wildfires swept through forests in the Greater Khingan mountains. But the flames didn’t fry the bacteria directly. Rather, the fire dramatically altered the soil biochemistry, most importantly changing its pH but also impacting moisture content, carbon/nitrogen ratio’s and ammonium levels.

This meant that the classes of bacteria that were more flexible at growing at an increased pH – like Bacteriodetes and Betaproteobacteria – were able to persist in the soil after the wildfire had swept through. The populations of other bacteria, like Acidobacteria, plummeted, since they were less equipped to grow in their newly scorched and acidified home.

It took 11 years for the original community of bacterial species to re-establish themselves. While this seems staggering, it’s actually a lot quicker than the above ground vegetation, which typically takes 20-100 years to reappear. Intriguingly, the bounce back of soil bacteria and the gradual re-emergence of a happy soil environment probably plays a huge role in the re-establishment of plants, and the animals that eat them.

This research may help to guide environmental efforts by aiming to adjust soil environments to help ecosystems make a speedy recovery after a wildfire.

Xiang, X., Shi, Y., Yang, J., Kong, J., Lin, X., Zhang, H., Zeng, J., & Chu, H. (2014). Rapid recovery of soil bacterial communities after wildfire in a Chinese boreal forest Scientific Reports, 4 DOI: 10.1038/srep03829

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